A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma That Has Spread to the Brain

ID: NCT02308020
Status: Recruiting
Phase: Phase 2
Start Date: April 01, 2015
First Submitted: December 02, 2014
Last Updated: February 14, 2018
Results: N/A
Organization: Eli Lilly and Company
Sponsors & Collaborators: Eli Lilly and Company
Location: Australia, Austria, Belgium, Canada, France, Israel, Italy, Spain, United States
Conditions: Breast Cancer, Non-small Cell Lung Cancer, Melanoma, Brain Metastases
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Study Description

Brief Summary

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as abemaciclib in participants with hormone receptor positive breast cancer, non-small cell lung cancer (NSCLC), or melanoma that has spread to the brain.

Detailed Description

Condition or disease Intervention/treatment Phase

Brain Metastases

Breast Cancer

Melanoma

Non-small Cell Lung Cancer

Drug: Abemaciclib
Other Names
LY2835219
Phase 2

Tracking Information

First Submitted DateDecember 02, 2014
Last Update Posted DateFebruary 14, 2018
Start DateApril 01, 2015
Anticipated Completion DateOctober 01, 2018
Primary Completion DateOctober 01, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR) [Time Frame: Baseline to Objective Disease Progression (Approximately 6 Months)]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Percentage of Participants with CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) [Time Frame: Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Approximately 6 Months)]

  • Duration of CR and PR: Duration of Intracranial Response (DOIR) [Time Frame: Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death from Any Cause (Approximately 6 Months)]

  • Proportion of Participants with BOIR of CR, PR, or SD: Intracranial Disease Control Rate (IDCR) [Time Frame: Baseline to Disease Progression or Start of New Anticancer Therapy (Approximately 6 Months)]

  • Proportion of Participants with BOIR of CR, PR, or SD with Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR) [Time Frame: Baseline to Disease Progression or Start of New Anticancer Therapy (Approximately 6 Months)]

  • Overall Survival [Time Frame: Baseline to Death from Any Cause (Approximately 18 Months)]

  • Percentage of Participants with a Best Response of CR or PR: Objective Response Rate (ORR) [Time Frame: Baseline to Disease Progression (Approximately 6 Months)]

  • Proportion of Participants with a Best Overall Response of CR, PR, or SD: Disease Control Rate (DCR) [Time Frame: Baseline to Disease Progression or Start of New Anticancer Therapy (Approximately 6 Months)]

  • Progression Free Survival [Time Frame: Baseline to Objective Disease Progression or Death from Any Cause (Approximately 6 Months)]

  • Change from Baseline to End of Study in Neurologic Symptoms on the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) Scale [Time Frame: Baseline, End of Study (Approximately 6 Months)]

  • Pharmacokinetics (PK): Minimum Concentration (Cmin) of Abemaciclib and its Metabolites [Time Frame: Cycle 1 through Cycle 4 (Approximately 3 Months)]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleA Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma That Has Spread to the Brain
Official TitleA Phase 2 Study of Abemaciclib in Patients With Brain Metastases Secondary to Hormone Receptor Positive Breast Cancer, Non-small Cell Lung Cancer, or Melanoma
Brief Summary

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as abemaciclib in participants with hormone receptor positive breast cancer, non-small cell lung cancer (NSCLC), or melanoma that has spread to the brain.

Detailed Description

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
247
Allocation
Non-Randomized
Interventional Model
Single Group Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Brain Metastases
Breast Cancer
Melanoma
Non-small Cell Lung Cancer
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Abemaciclib

Administered orally

Other Names
LY2835219
Study Groups/Cohorts
Part A: HER2+ Breast Cancer
Participants with HR+, HER2+ breast cancer. 200 milligrams (mg) abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Part B: HER2- Breast Cancer
Participants with HR+, HER2- breast cancer. 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Part C: Surgical Resection
Participants with HR+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated. 200 mg abemaciclib given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Part D: NSCLC
Participants with NSCLC. 200 milligrams mg (150 mg for participants receiving concurrent gemcitabine or pemetrexed) abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Part E: Melanoma
Participants with melanoma. 200 milligrams mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Part F: HR+ Breast Cancer, NSCLC, or Melanoma
Participants with HR+ breast cancer, NSCLC, or melanoma and leptomeningeal metastases. 200 milligrams mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Study Arms
Experimental Part A: HER2+ Breast Cancer
Participants with HR+, HER2+ breast cancer. 200 milligrams (mg) abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Experimental Part B: HER2- Breast Cancer
Participants with HR+, HER2- breast cancer. 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Experimental Part C: Surgical Resection
Participants with HR+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated. 200 mg abemaciclib given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Experimental Part D: NSCLC
Participants with NSCLC. 200 milligrams mg (150 mg for participants receiving concurrent gemcitabine or pemetrexed) abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Experimental Part E: Melanoma
Participants with melanoma. 200 milligrams mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Experimental Part F: HR+ Breast Cancer, NSCLC, or Melanoma
Participants with HR+ breast cancer, NSCLC, or melanoma and leptomeningeal metastases. 200 milligrams mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Administered orally

Arm Intervention/Treatment
Experimental Part A: HER2+ Breast Cancer
Participants with HR+, HER2+ breast cancer. 200 milligrams (mg) abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Experimental Part B: HER2- Breast Cancer
Participants with HR+, HER2- breast cancer. 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Experimental Part C: Surgical Resection
Participants with HR+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated. 200 mg abemaciclib given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Experimental Part D: NSCLC
Participants with NSCLC. 200 milligrams mg (150 mg for participants receiving concurrent gemcitabine or pemetrexed) abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Experimental Part E: Melanoma
Participants with melanoma. 200 milligrams mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib
Experimental Part F: HR+ Breast Cancer, NSCLC, or Melanoma
Participants with HR+ breast cancer, NSCLC, or melanoma and leptomeningeal metastases. 200 milligrams mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Abemaciclib

Recruitment Information

Recruitment Status:Recruiting
Enrollment247
Completion DateOctober 01, 2018
Eligibility Criteria: Inclusion Criteria:
- Have brain metastases secondary to hormone receptor positive breast cancer, NSCLC, or melanoma.
- Have either human epidermal growth factor receptor 2 positive (HER2+) (Study Part A) or HER2- (Study Part B) breast cancer.
- Participants in Study Part C must have HR+ breast cancer, NSCLC, or melanoma with brain lesions clinically indicated for surgical resection as well as consent to provide tissue for drug concentration determination after 5 to 14 days of study drug dosing.
- Participants in Part D must have NSCLC of any subtype.
- Participants in Part E must have melanoma of any subtype.
- Participants in Part F must have HR+ breast cancer, NSCLC, or melanoma with leptomeningeal metastases.
- For Parts A, B, D, and E: Must have at least 1 measurable brain lesion ≥10 millimeters (mm) in the longest diameter (LD).
- For Part C (surgical): Have metastatic brain lesion(s) for which surgical resection is clinically indicated.
- Have completed local therapy (surgical resection, WBRT, or SRS) ≥14 days prior to initiating abemaciclib and recovered from all acute effects.
- If receiving concomitant corticosteroids, must be on a stable or decreasing dose for at least 7 days prior to the baseline Gd-MRI.
- Have a Karnofsky performance status of ≥70.
- Have a life expectancy ≥12 weeks.
- For HR+ breast cancer participants in part A, B, C, and F: If currently receiving endocrine therapy, a participant may continue to receive the same endocrine therapy provided that extracranial disease is stable for at least 3 months and central nervous system (CNS) disease progression has occurred while on this endocrine therapy. If these conditions are not met, participants must discontinue endocrine therapy prior to initiation of abemaciclib.
- For HER2+ breast cancer participants in parts A, C, and F: participants may receive concurrent treatment (ongoing or initiated simultaneously with abemaciclib) with IV trastuzumab.
- For NSCLC participants in parts C, D, and F: if currently receiving gemcitabine or pemetrexed (single-agent or in combination with another therapy), a participant may continue to receive 1 of these 2 therapies provided that extracranial disease is stable for at least 6 weeks and CNS disease progression has occurred while on this therapy.
- Have adequate organ function.

Exclusion Criteria:
- Require immediate local therapy, including but not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases.
- Are taking concurrent enzyme-inducing antiepileptic drugs (EIAED).
- Have evidence of significant (ie, symptomatic) intracranial hemorrhage.
- For Parts A, B, C, D, E: Have evidence of leptomeningeal metastases. Note: discrete dural metastases are permitted.
- Have experienced >2 seizures within 4 weeks prior to study entry.
- For Parts A, B, D, E, and F: Have previously received treatment with any cyclin dependent kinase 6 (CDK6) inhibitor. For Part C participants may have received prior palbociclib or ribociclib, but not abemaciclib treatment.
- Have known contraindication to Gd-MRI.
- Have a preexisting chronic condition resulting in persistent diarrhea.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Australia
Austria
Belgium
Canada
France
Israel
Italy
Spain
United States
New Zealand

Administrative Information

NCT Number:NCT02308020
Other Study ID Numbers
15450
I3Y-MC-JPBO
2014-004010-28
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Eli Lilly and Company
Collaborators
Not Available
Investigators
Study Director
Call 1-877-CTLILLY (1-877-285-459) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company